Cone beam CT doses in radiotherapy patient positioning in Finland-prostate treatments.

Imaging parameters, frequencies and resulting patient organ doses in treatments of prostate cancer were assessed in Finnish radiotherapy centres. Based on a questionnaire to the clinics, Monte Carlo method was used to estimate organ doses in International Commission on Radiological Protection standard phantom for prostate, bladder, rectum and femoral head. The results show that doses from cone beam computed tomography imaging have reduced compared to earlier studies and are between 3.6 and 34.5 mGy per image for the above-mentioned organs and for normal sized patients. There still is room for further optimization of the patient exposure, as many centres use the default imaging parameters, and the length of the imaged region may not be optimal for the purpose.

Limited Role for Routine Restaging After Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

BACKGROUND: Although many patients with locally advanced rectal cancer undergo restaging imaging after neoadjuvant chemoradiotherapy and before surgery, the benefit of this practice is unclear. The purpose of this study was to examine the impact of reimaging on outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of consecutive patients with stage 2 and 3 rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy between May 2005 and April 2018. Patient and disease characteristics, imaging, treatment, and oncologic outcomes were compared between those who underwent restaging and those who went directly to surgery. Predictors of outcomes and cost effectiveness of restaging were determined. RESULTS: Of 224 patients, 146 underwent restaging. Six restaged patients had findings leading to a change in management. There was no difference in freedom from recurrence (P = 0.807) and overall survival (P = 0.684) based on restaging. Pretreatment carcinoembryonic antigen level >3 ng/mL (P = 0.010), clinical T stage 4 (P = 0.016), and pathologic T4 (P = 0.047) and N2 (P = 0.002) disease increased the risk of death, whereas adjuvant chemotherapy decreased the risk of death (P < 0.001) on multivariate analysis. Disease recurrence was lower with pelvic exenteration (P = 0.005) and in females (P = 0.039) and higher with pathologic N2 (P = 0.003) and N3 (P = 0.002) disease. The average cost of reimaging is $40,309 per change in management; however, $45 is saved per patient when downstream surgical costs are considered. CONCLUSIONS: Imaging restaging after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer rarely changes treatment and does not improve survival. In a subset of patients at higher risk for worse outcome, reimaging may be beneficial.

RapidBrachyDL: Rapid Radiation Dose Calculations in Brachytherapy Via Deep Learning.

PURPOSE: Detailed and accurate absorbed dose calculations from radiation interactions with the human body can be obtained with the Monte Carlo (MC) method. However, the MC method can be slow for use in the time-sensitive clinical workflow. The aim of this study was to provide a solution to the accuracy-time trade-off for 192Ir-based high-dose-rate brachytherapy by using deep learning. METHODS AND MATERIALS: RapidBrachyDL, a 3-dimensional deep convolutional neural network (CNN) model, is proposed to predict dose distributions calculated with the MC method given a patient's computed tomography images, contours of clinical target volume (CTV) and organs at risk, and treatment plan. Sixty-one patients with prostate cancer and 10 patients with cervical cancer were included in this study, with data from 47 patients with prostate cancer being used to train the model. RESULTS: Compared with ground truth MC simulations, the predicted dose distributions by RapidBrachyDL showed a consistent shape in the dose-volume histograms (DVHs); comparable DVH dosimetric indices including 0.73% difference for prostate CTV D90, 1.1% for rectum D2cc, 1.45% for urethra D0.1cc, and 1.05% for bladder D2cc; and substantially smaller prediction time, acceleration by a factor of 300. RapidBrachyDL also demonstrated good generalization to cervical data with 1.73%, 2.46%, 1.68%, and 1.74% difference for CTV D90, rectum D2cc, sigmoid D2cc, and bladder D2cc, respectively, which was unseen during the training. CONCLUSION: Deep CNN-based dose estimation is a promising method for patient-specific brachytherapy dosimetry. Desired radiation quantities can be obtained with accuracies arbitrarily close to those of the source MC algorithm, but with much faster computation times. The idea behind deep CNN-based dose estimation can be safely extended to other radiation sources and tumor sites by following a similar training process.

A randomised assessment of image guided radiotherapy within a phase 3 trial of conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: Image-guided radiotherapy (IGRT) improves treatment set-up accuracy and provides the opportunity to reduce target volume margins. We introduced IGRT methods using standard (IGRT-S) or reduced (IGRT-R) margins in a randomised phase 2 substudy within CHHiP trial. We present a pre-planned analysis of the impact of IGRT on dosimetry and acute/late pelvic side effects using gastrointestinal and genitourinary clinician and patient-reported outcomes (PRO) and evaluate efficacy. MATERIALS AND METHODS: CHHiP is a randomised phase 3, non-inferiority trial for men with localised prostate cancer. 3216 patients were randomly assigned to conventional (74 Gy in 2 Gy/fraction (f) daily) or moderate hypofractionation (60 or 57 Gy in 3 Gy/f daily) between October 2002 and June 2011. The IGRT substudy included a second randomisation assigning to no-IGRT, IGRT-S (standard CTV-PTV margins), or IGRT-R (reduced CTV-PTV margins). Primary substudy endpoint was late RTOG bowel and urinary toxicity at 2 years post-radiotherapy. RESULTS: Between June 2010 to July 2011, 293 men were recruited from 16 centres. Median follow-up is 56.9(IQR 54.3-60.9) months. Rectal and bladder dose-volume and surface percentages were significantly lower in IGRT-R compared to IGRT-S group; (p < 0.0001). Cumulative proportion with RTOG grade ≥ 2 toxicity reported to 2 years for bowel was 8.3(95% CI 3.2-20.7)%, 8.3(4.7-14.6)% and 5.8(2.6-12.4)% and for urinary 8.4(3.2-20.8)%, 4.6(2.1-9.9)% and 3.9(1.5-9.9)% in no IGRT, IGRT-S and IGRT-R groups respectively. In an exploratory analysis, treatment efficacy appeared similar in all three groups. CONCLUSION: Introduction of IGRT was feasible in a national randomised trial and IGRT-R produced dosimetric benefits. Overall side effect profiles were acceptable in all groups but lowest with IGRT and reduced margins. ISRCTN: 97182923.

Assessing localized dosimetric effects due to unplanned gas cavities during pelvic MR-guided radiotherapy using Monte Carlo simulations.

PURPOSE: It has been proposed that beam modulation and opposing beam configurations can cancel effects of the Electron Return Effect (ERE) during MR-guided radiotherapy (MRgRT). However, this may not always be the case for unplanned gas cavities outside of the target in the pelvic region. We evaluate dosimetric effects, including effects in the rectal wall, due to unplanned spherical air cavities during MRgRT. METHODS: Nine virtual cuboid water phantoms containing spherical air cavities (0.5-7.5 cm diameter) and a reference phantom without air were created. Monte Carlo dose calculations of 7 MV photons under the influence of a 1.5 T transverse magnetic field were produced using Monaco 5.19.02 Treatment Planning System (TPS) (Elekta AB, Stockholm, Sweden). Cavities in the path of a single and multiple beam plans were considered. Dose distributions of phantoms with and without air cavities were compared (ΔD% ) using a spherical coordinate system originating in the center of the cavity. Effects in the rectal wall were quantified by comparing dose volume histogram (DVH) parameters for solid and gaseous filling from simulated rectal wall structures. RESULTS: Max(ΔD% ) of ~70% and 20% were observed around large cavities in the path of a single and multiple beam plans, respectively. Approximately 45 cm3 of phantom surrounding the largest cavity in a single beam received dose changes of >10%. Dmean in the rectal wall was unchanged when comparing gaseous and solid filling in the path of a single beam; however, D1cc and Dmax increased by up to ~45% and ~63%, respectively. CONCLUSIONS: Unplanned gas cavities in the path of a single beam during pelvic MRgRT with a 1.5 T transverse magnetic field cause dose changes which may impact toxicity in the rectal wall, depending on local dose and fractionation. Effects are reduced but not eliminated with a five-beam plan.

Dosimetric Considerations for Ytterbium-169, Selenium-75, and Iridium-192 Radioisotopes in High-Dose-Rate Endorectal Brachytherapy.

PURPOSE: To investigate differences between prescribed and postimplant calculated dose in 192Ir high-dose-rate endorectal brachytherapy (HDR-EBT) by evaluating dose to clinical target volume (CTV) and organs at risk (OARs) calculated with a Monte Carlo-based dose calculation software, RapidBrachyMC. In addition, dose coverage, conformity, and homogeneity were compared among the radionuclides 192Ir, 75Se, and 169Yb for use in HDR-EBT. METHODS AND MATERIALS: Postimplant dosimetry was evaluated using 23 computed tomography (CT) images from patients treated with HDR-EBT using the 192Ir microSelectron v2 (Elekta AB, Stockholm, Sweden) source and the Intracavitary Mold Applicator Set (Elekta AB, Stockholm, Sweden), which is a flexible applicator capable of fitting a tungsten rod for OAR shielding. Four tissue segmentation schemes were evaluated: (1) TG-43 formalism, (2) materials and nominal densities assigned to contours of foreign objects, (3) materials and nominal densities assigned to contoured organs in addition to foreign objects, and (4) materials specified as in (3) but with voxel mass densities derived from CT Hounsfield units. Clinical plans optimized for 192Ir were used, with the results for 75Se and 169Yb normalized to the D90 of the 192Ir clinical plan. RESULTS: In comparison to segmentation scheme 4, TG-43-based dosimetry overestimates CTV D90 by 6% (P = .00003), rectum D50 by 24% (P = .00003), and pelvic bone D50 by 5% (P = .00003) for 192Ir. For 169Yb, CTV D90 is overestimated by 17% (P = .00003) and rectum D50 by 39% (P = .00003), and pelvic bone D50 is significantly underestimated by 27% (P = .007). Postimplant dosimetry calculations also showed that a 169Yb source would give 20% (P = .00003) lower rectum V60 and 17% (P = .00008) lower rectum D50. CONCLUSIONS: Ignoring high-Z materials in dose calculation contributes to inaccuracies that may lead to suboptimal dose optimization and disagreement between prescribed and calculated dose. This is especially important for low-energy radionuclides. Our results also show that with future magnetic resonance imaging-based treatment planning, loss of CT density data will only affect calculated dose in nonbone OARs by 2% or less and bone OARs by 13% or less across all sources if material composition and nominal mass densities are correctly assigned.

Sequential simulation computed tomography allows assessment of internal rectal movements during preoperative chemoradiotherapy in rectal cancer.

PURPOSES: The purpose of this study was to assess the internal rectal movement and to determine the factors related to extensive internal rectal movement using sequential simulation computed tomography (CT) images. MATERIALS AND METHODS: From 2010 to 2015, 96 patients receiving long-course preoperative chemoradiotherapy were included in our retrospective study. The initial simulation CT (Isim-CT) and follow-up simulation CT (Fsim-CT) for a boost were registered according to the isocenters and bony structure. The rectums on Isim-CT and Fsim-CT were compared on four different axial planes as follows: (1) lower pubis symphysis (AXVERYLOW), (2) upper pubis symphysis (AXLOW), (3) superior rectum (AXHIGH), and (4) middle of AXLOW and AXHIGH (AXMID). The involved rectum in the planning target volume was evaluated. The maximal radial distances (MRD), the necessary radius from the end of Isim-CT rectum to cover entire Fsim-CT rectum, and the common area rate (CAR) of the rectum (CAR, (Isim-CT∩Fsim-CT)/(Isim-CT)) were measured. Linear regression tests for the MRDs and logistic regression tests for the CARs were conducted. RESULTS: The mean ± standard deviation (mm) of MRDs and CAR <80% for AXVERYLOW, AXLOW, AXMID, and AXHIGH were 2.3 ± 2.5 and 8.9%, 3.0 ± 3.7 and 17.4%, 4.0 ± 5.2 and 27.1%, and 4.1 ± 5.2 and 25%, respectively. For MRDs and CARs, a higher axial level (AXVERYLOW/AXMID-HIGH, P = 0.018 and P = 0.034, respectively), larger bladder volume (P = 0.054 and P = 0.017, respectively), smaller bowel gas extent (small/marked, P = 0.014 and P = 0.001, respectively), and increased bowel gas change (decrease/increase, both P < 0.001) in rectum were associated with extensive internal rectal movement in multivariate analyses. CONCLUSIONS: As a result of following internal rectal movement through sequential simulation CT, the rectum above the pubis symphysis needs a larger margin, and bladder volume and bowel gas should be closely observed.

Application of aSi-kVCBCT for Volume Assessment and Dose Estimation: An Offline Adaptive Study for Prostate Radiotherapy

Objective: The purpose of this study is to develop a method to estimate the dose using amorphous silicon detector panel cone beam computed tomography (aSi-kVCBCT) for the OARs and targets in prostate radiotherapy and to compare with the actual planned dose. Methods: The aSi-kVCBCT is used widely in radiotherapy to verify the patient position before treatment. The advancement in aSi-kVCBCT combined with adaptive software allows us to verify the dose distribution in daily acquired CBCT images. CBCT images from 10 patients undergoing radical prostate radiotherapy were included in this study. Patients received total dose of 65Gy in 25 fractions using volumetric modulated arc therapy (VMAT). aSi-kVCBCT scans were acquired before daily treatment and exported to smart adapt software for image adaptation. The planning CT is adapted to daily aSi-kVCBCT images in terms of HU mapping. The primary VMAT plans were copied on to the adapted planning CT images and dose was calculated using Anisotropic Analytic Algorithm (AAA). The DVH is then used to evaluate the volume changes of organs at risk (OAR), the actual dose received by OARs, CTV and PTV during a single fraction. Results: The normalized volume of the bladder and rectum ranged from 0.70­1.66 and 0.70­1.16 respectively. The cumulative mean Sorensen­Dice coefficient values of bladder and rectum were 0.89±0.04 and 0.79±0.06 respectively. The maximum dose differences for CTV and PTV were 2.5% and -4.7% and minimum were 0.1% and 0.1% respectively. Conclusion: The adapted planning CT obtained from daily imaging using aSi-kVCBCT and SmartAdapt® can be used as an effective tool to estimate the volume changes and dose difference in prostate radiotherapy.

Evaluating the Cost-Effectiveness of Hydrogel Rectal Spacer in Prostate Cancer Radiation Therapy.

PURPOSE: A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT). METHODS AND MATERIALS: A multistate Markov model was constructed from the U.S. payer perspective to examine the cost-effectiveness of HRS in men with localized PC receiving EBRT (EBRT alone vs EBRT + HRS). The subgroups analyzed included site of HRS placement (hospital outpatient, physician office, ambulatory surgery center) and proportion of patients with good baseline erectile function (EF). Data on EF, gastrointestinal and genitourinary toxicities incidence, and potential risks associated with HRS implantation were obtained from a recently published randomized clinical trial. Health utilities and costs were derived from the literature and the 2018 Physician Fee Schedule and were discounted 3% annually. Quality-adjusted life years (QALYs) and costs were modeled for a 5-year period from receipt of RT. Probabilistic sensitivity analysis and value-based threshold analyses were conducted. RESULTS: The per-patient 5-year incremental cost for spacers administered in a hospital outpatient setting was $3578, and the incremental effectiveness was 0.0371 QALYs. The incremental cost-effectiveness ratio was $96,440/QALY for patients with PC undergoing HRS insertion in a hospital and $39,286/QALY for patients undergoing HRS insertion in an ambulatory facility. For men with good baseline EF, the incremental cost-effectiveness ratio was $35,548/QALY and $9627/QALY in hospital outpatient and ambulatory facility settings, respectively. CONCLUSIONS: Based on the current Medicare Physician Fee Schedule, HRS is cost-effective at a willingness to pay threshold of $100,000. These results contain substantial uncertainty, suggesting more evidence is needed to refine future decision-making.

A novel rectal applicator for contact radiotherapy with HDR 192Ir sources.

PURPOSE: Dose escalation to rectal tumors leads to higher complete response rates and may thereby enable omission of surgery. Important advantages of endoluminal boosting techniques include the possibility to apply a more selective/localized boost than using external beam radiotherapy. A novel brachytherapy (BT) rectal applicator with lateral shielding was designed to be used with a rectoscope for eye-guided positioning to deliver a dose distribution similar to the one of contact x-ray radiotherapy devices, using commonly available high-dose-rate 192Ir BT sources. METHODS AND MATERIALS: A cylindrical multichannel BT applicator with lateral shielding was designed by Monte Carlo modeling, validated experimentally with film dosimetry and compared with results found in the literature for the Papillon 50 (P50) contact x-ray radiotherapy device regarding rectoscope dimensions, radiation beam shape, dose fall-off, and treatment time. RESULTS: The multichannel applicator designed is able to deliver 30 Gy under 13 min with a 20350 U (5 Ci) source. The use of multiple channels and lateral shielding provide a uniform circular treatment surface with 22 mm in diameter. The resulting dose fall-off is slightly steeper (maximum difference of 5%) than the one generated by the P50 device with the 22 mm applicator. CONCLUSIONS: A novel multichannel rectal applicator for contact radiotherapy with high-dose-rate 192Ir sources that can be integrated with commercially available treatment planning systems was designed to produce a dose distribution similar to the one obtained by the P50 device.

Assessment of cartesian co-ordinates-based bladder and rectal dose and variability with tandem-ring angles first Nigerian experience in high-dose-rate brachytherapy.

OBJECTIVE:: This study assessed bladder and rectal dose based on Cartesian-coordinates in intracavitary brachytherapy and examined the variations resulting from use of tandem-ring (T-R) of different angles. METHODS:: Cartesian-co-ordinates of bladder and rectum points were derived on orthogonal-radiographs of 90 patients who had high-dose-rate brachytherapy for cervical cancer at the Department of Radiation Oncology, University College Hospital, Ibadan, Nigeria. The patients were classified in three groups of 30, based on T-R angles 30°, 45° and 60° used, bearing same lengths and diameters across sets. The measured co-ordinates and the related percentage doses to points of interest in the two organs were analysed using EViews and SPSS statistical softwares. RESULTS:: The mean rectal point dose (RPD) obtained was 68.97 ± 13.57 % of the prescribed doses as against 56.57 ± 11.83% for bladder point dose. While the maximums of the mean RPD were 95.7, 90.5 and 82.5% for T-R angles 30°, 45° and 60° respectively; corresponding values for the bladder point were 72.8, 87.8 and 62.3%. CONCLUSION:: The baseline data obtained in this study served as guidelines for subsequently achieving acceptable values of bladder point dose and RPD at University College Hospital, Nigeria. Special attention should be paid to the application of 2 cm-tandems in relation to the RPD. ADVANCES IN KNOWLEDGE:: This is one of the few studies assessing the influence of T-R angles on organs-at-risk. The increase in RPD with the use of intrauterine tandem-2 cm is found to be most pronounced with T-R 300, and this trend reduced with larger angles.

Development and Preliminary Evaluation of a Murine Model of Chronic Radiation-Induced Proctitis.

PURPOSE: Radiotherapy (RT) is commonly used to treat most pelvic malignancies. While treatment is often effective, curative radiation doses to the rectum can result in chronic radiation-induced proctitis, which is characterized by diarrhea, tenesmus, and/or rectal bleeding, recently termed pelvic radiation disease. An animal model of chronic radiation-induced proctitis would be useful to test both preventative and therapeutic strategies to limit this morbidity but has been elusive because of the high rodent mortality associated with acute bowel RT injury. The objective of this research was to develop a novel mouse model of chronic radiation-induced proctitis using advanced technology. METHODS AND MATERIALS: Using an X-RAD 225-Cx (Precision X-Ray) small animal irradiator, multiple plan configurations were evaluated for planning treatment volume and organ-at-risk avoidance to deliver a 15 Gy 3D conformal treatment plan. The final plan was verified by high resolution 3D dosimetry (PRESAGE/optical-CT), and delivered using a single arc. Mice were monitored for mortality for 250 days, followed by histopathological correlates including mucicarmine, Masson's trichrome, and fecal pellet length. RESULTS: Six beam arrangements were considered: single and parallel-opposed fields with whole-pelvis coverage, and collimated fields in parallel-opposed, 3-field, 4-field, and arc geometries. A collimated arc plan offered superior planning treatment volume coverage and organ-at-risk avoidance compared to whole-pelvis irradiation. Treatment verification with PRESAGE 3D dosimetry (Heuris Inc) showed >99% of voxels passing gamma analysis with 2%/2 mm criteria. Our treatment resulted in no acute mortality and 40% mortality at 250 days. Histopathological analysis showed increased mucous production and fibrosis of the irradiated colon, but no change in fecal pellet length. CONCLUSIONS: Our model was able to target successfully lower colon and rectum with lower mortality than other published models. This permitted measurement of late effects that recapitulate some features of rectal damage in humans.

Radiotherapy of rectal cancer in elderly patients: Real-world data assessment in a decade.

BACKGROUND AND PURPOSE: There is paucity of data on the efficacy and toxicity of radiotherapy in rectal cancer (RC) elderly patients. The objective was to identify management strategies and resulting outcomes in RC patients ≥70 years undergoing radiotherapy. MATERIAL AND METHODS: A retrospective study included consecutive RC patients ≥70 years undergoing rectal radiotherapy. RESULTS: From 2004-2015, 340 RC patients underwent pre-operative (n = 238; 70%), post-operative (n = 41, 12%), or exclusive (n = 61, 18%) radiotherapy, with a median age of 78.5 years old (range: 70-96). Radiotherapy protocols were tailored, with 54 different radiotherapy programs (alteration of the total dose, and/or fractionation, and/or volume). Median follow-up was 27.1 months. Acute and late grade 3-4 radio-induced toxicities were reported in 3.5% and 0.9% of patients. Metastatic setting (OR = 6.60, CI95% 1.47-46.03, p = 0.02), exclusive radiotherapy (OR = 5.08, CI95% 1.48-18.21, p = 0.009), and intensity-modulated radiotherapy (OR = 6.42, CI95% 1.31-24.73, p = 0.01) were associated with grade ≥3 acute toxicities in univariate analysis. Exclusive radiotherapy (OR = 9.79, CI95% 2.49-43.18, p = 0.001) and intensity-modulated radiotherapy (OR = 12.62, CI95% 2.05-71.26, p = 0.003) were independent predictive factors of grade ≥3 acute toxicities in multivariate analysis. A complete pathological response was achieved in 12 out of 221 pre-operative patients (5.4%). Age, tumor stage, and surgery were independent predictive factors of survival in multivariate analysis. At end of follow-up, 7.1% of patients experienced local relapse. CONCLUSION: Radiotherapy for RC in elderly patients appeared safe and manageable, perhaps due to the tailoring of radiotherapy protocols. Tailored management resulted in acceptable rate of local tumor control.

Hydrogel spacers in prostate radiotherapy: a promising approach to decrease rectal toxicity.

High-dose radiation is a well-established method of treatment for prostate cancer. The main limiting structure for dose escalation is the rectum. The risk of rectal toxicity is related to dose received by the rectum. Several strategies for reducing dose to rectum have been explored; these include endorectal balloons as well as injection of rectal spacers like hydrogels. They create greater distance between rectal wall and prostate to confer a dosimetric advantage to the rectum. Early clinical studies with hydrogels have shown favorable outcomes. A low incidence of major procedural adverse effects with hydrogel use has been reported and it is well tolerated by patients. Hydrogel holds promise in establishing itself as an adjunct to standard of care in prostate radiation.

Biological dose and complication probabilities for the rectum and bladder based on linear energy transfer distributions in spot scanning proton therapy of prostate cancer.

BACKGROUND: The increased linear energy transfer (LET) at the end of the Bragg peak causes concern for an elevated and spatially varying relative biological effectiveness (RBE) of proton therapy (PT), often in or close to dose-limiting normal tissues. In this study, we investigated dose-averaged LET (LETd) distributions for spot scanning PT of prostate cancer patients using different beam angle configurations. In addition, we derived RBE-weighted (RBEw) dose distributions and related normal tissue complication probabilities (NTCPs) for the rectum and bladder. MATERIAL AND METHODS: A total of 21 spot scanning proton plans were created for each of six patients using a prescription dose of 78 Gy(RBE1.1), with each plan using two 'mirrored' beams with gantry angles from 110°/250° to 70°/290°, in steps of 2°. Physical dose and LETd distributions were calculated as well as RBEw dose distributions using either RBE = 1.1 or three different variable RBE models. The resulting biological dose distributions were used as input to NTCP models for the rectum and bladder. RESULTS: For anterior oblique (AO) configurations, the rectum LETd volume and RBEw dose increased with increasing angles off the lateral opposing axis, with the RBEw rectum dose being higher than for all posterior oblique (PO) configurations. For PO configurations, the corresponding trend was seen for the bladder. Using variable RBE models, the rectum NTCPs were highest for the AO configurations with up to 3% for the 80°/280° configuration while the bladder NTCPs were highest for the PO configurations with up to 32% for the 100°/260°. The rectum D1cm3 constraint was fulfilled for most patients/configurations when using uniform RBE but not for any patient/configuration with variable RBE models. CONCLUSIONS: Compared to using constant RBE, the variable RBE models predicted increased biological doses to the rectum, bladder and prostate, which in turn lead to substantially higher estimated rectum and bladder NTCPs.

Development of a virtual spacer to support the decision for the placement of an implantable rectum spacer for prostate cancer radiotherapy: Comparison of dose, toxicity and cost-effectiveness.

INTRODUCTION: Previous studies have shown that the implantable rectum spacer (IRS) is not beneficial for all patients. A virtual IRS (V-IRS) was constructed to help identify the patients for whom it is cost-effective to implant an IRS, and its viability as a tool to tailor the decision of an IRS implantation to be beneficial for the specified patient was assessed. Please watch animation: (https://www.youtube.com/watch?v=tDlagSXMKqw) MATERIALS AND METHODS: The V-IRS was tested on 16 patients: 8 with a rectal balloon implant (RBI) and 8 with a hydrogel spacer. A V-IRS was developed using 7 computed tomography (CT) scans of patients with a RBI. To examine the V-IRS, CT scans before and after the implantation of an IRS were used. IMRT plans were made based on CT scans before the IRS, after IRS and with the V-IRS, prescribing 70 Gray (Gy) to the planning target volume. Toxicity was accessed using externally validated normal tissue complication probability (NTCP) models, and the Cost-effectiveness was analyzed using a published Markov model. RESULTS: The rectum volume receiving 75Gy (V75) were improved by both the IRS and the V-IRS with on average 4.2% and 4.3% respectively. The largest NTCP reduction resulting from the IRS and the V-IRS was 4.0% and 3.9% respectively. The RBI was cost-effective for 1 out of 8 patients, and the hydrogel was effective for 2 out of 8 patients, and close to effective for a third patient. The classification accuracy of the model, regarding cost-effectiveness, was 100%. CONCLUSION: The V-IRS approach in combination with a toxicity prediction model and a cost-effectiveness analyses is a promising basis for a decision support tool for the implantation of either a hydrogel spacer or a rectum balloon implant.

Local Hypothermia as a Radioprotector of the Rectal Wall During Prostate Stereotactic Body Radiation Therapy.

PURPOSE: To compare the single-fraction dose-related incidence of rectal obstruction and/or bleeding in normothermic and hypothermic rectums of a rat model. METHODS AND MATERIALS: A 1.9-cm length of rectum was irradiated with a single fraction in 57 Sprague-Dawley rats using a dedicated image-guided small animal irradiator and Monte Carlo-based treatment planning system. All rats had a rectal temperature control apparatus placed during irradiation and were stratified to achieve either a normothermic (37°C) or hypothermic (15°C) rectal wall temperature. Radiation was delivered to a 1-cm-diameter cylindrical volume about the cooling device and rectal wall. The radiation dose was escalated from 16 Gy up to 37 Gy to assess the dose response in each arm. The primary endpoint of this study was rectal obstruction and/or bleeding during a follow-up of 180 to 186 days. Histologic scoring was performed on all study rats. RESULTS: Probit analysis showed a dose associated with a 50% incidence of rectal obstruction of 24.6 Gy and 40.8 Gy for normothermic and hypothermic arms, respectively. The occurrence of obstruction and/or bleeding correlated with the posttreatment histologic score for normothermic rats; however, there was no difference in histologic score between normothermic and hypothermic rats at the highest dose levels evaluated. CONCLUSIONS: A significant radioprotective effect was observed using local hypothermia during a single large dose of radiation for the functional endpoint of rectal obstruction and/or bleeding. A confirmatory study in a large animal model with anatomic and physiologic similarities to humans is suggested.

A Monte Carlo study of I-125 prostate brachytherapy with gold nanoparticles: dose enhancement with simultaneous rectal dose sparing via radiation shielding.

We investigate via Monte Carlo simulations a new 125I brachytherapy treatment technique for high-risk prostate cancer patients via injection of Au nanoparticle (AuNP) directly into the prostate. The purpose of using the nanoparticles is to increase the therapeutic index via two synergistic effects: enhanced energy deposition within the prostate and simultaneous shielding of organs at risk from radiation escaping from the prostate. Both uniform and non-uniform concentrations of AuNP are studied. The latter are modeled considering the possibility of AuNP diffusion after the injection using brachy needles. We study two extreme cases of coaxial AuNP concentrations: centered on brachy needles and centered half-way between them. Assuming uniform distribution of 30 mg g-1 of AuNP within the prostate, we obtain a dose enhancement larger than a factor of 2 to the prostate. Non-uniform concentration of AuNP ranging from 10 mg g-1 and 66 mg g-1 were studied. The higher the concentration in a given region of the prostate the greater is the enhancement therein. We obtain the highest dose enhancement when the brachytherapy needles are coincident with AuNP injection needles but, at the same time, the regions in the tail are colder (average dose ratio of 0.7). The best enhancement uniformity is obtained with the seeds in the tail of the AuNP distribution. In both uniform and non-uniform cases the urethra and rectum receive less than 1/3 dose compared to an analog treatment without AuNP. Remarkably, employing AuNP not only significantly increases dose to the target but also decreases dose to the neighboring rectum and even urethra, which is embedded within the prostate. These are mutually interdependent effects as more enhancement leads to more shielding and vice-versa. Caution must be paid since cold spot or hot spots may be created if the AuNP concentration versus seed position is not properly distributed respect to the seed locations.

Large-scale Retrospective Monte Carlo Dosimetric Study for Permanent Implant Prostate Brachytherapy.

PURPOSE: To retrospectively compare water-based and full tissue model Monte Carlo dose calculations in a large cohort of patients undergoing 125I permanent implant prostate brachytherapy. METHODS AND MATERIALS: For 613 patients, EGSnrc BrachyDose dose calculations were performed in 2 virtual patient models: TG43sim (simulated American Association of Physicists in Medicine Task Group Report 43 conditions) and MCref (computed tomography-derived heterogeneous tissue model with interseed effects). A sensitivity analysis was performed in a patient subset (25 with and 25 without prostatic calcifications) to explore dose calculation dependence on organ-at-risk (OAR) and calcification tissue elemental compositions and modelling approach. RESULTS: In the target volume, the minimum radiation dose delivered to 90% of prostate (D90) (volume of prostate receiving at least 100% of prescription dose [V100]) was lower with MCref than with TG43sim by 5.9% ± 1.6% (2.6% ± 1.7%), on average. Patients with prostatic calcifications can have substantial underdosed volumes due to calcification shielding, lowering the D90 by ≤25%. In the urethra, the average D5 (D30) was lower with MCref than with TG43sim by 4.4% ± 1.8% (4.7% ± 1.9%). In the rectum (bladder), the minimum dose to the hottest 0.1 cm3 (D_0.1cm3) of the contoured organ was lower (higher) with MCref than with TG43sim by 5.2% ± 1.8% (1.3% ± 1.8%). Doses to the target and OARs can increase or decrease by several percentages, depending on the assumed tissue elemental composition. In patients with calcifications, differences between approaches to model calcifications can change the target and OAR dose metrics by upward of 10%. CONCLUSIONS: TG43sim typically overestimates the target and OAR doses by several percentages, on average, compared with MCref. The considerable variation in the relative TG43sim and MCref doses between patients, and the larger dose differences for patients with calcification, suggests that clinical adoption of Monte Carlo dose calculations for permanent implant prostate brachytherapy should be pursued. The substantial sensitivity of the Monte Carlo dose calculations to the patient modelling approach supports the adoption of a consensus modelling scheme, such as MCref described in the present study, to ensure consistency of practice.

Feasibility evaluation of diffusion-weighted imaging using an integrated MRI-radiotherapy system for response assessment to neoadjuvant therapy in rectal cancer.

OBJECTIVE: To evaluate the feasibility of on-board diffusion-weighted imaging (DWI) with an integrated low-field MRI radiotherapy system to assess responses to neoadjuvant chemoradiation (NAC) in rectal cancer. METHODS: A spin echo-based planar imaging diffusion sequence on a 0.35-T MRI radiotherapy system was acquired over the course of NAC. The apparent diffusion coefficients (ADCs) from the tumour regions of interest (ROIs) were calculated. A functional diffusion map (fDM) was created showing a pixelwise ADC analysis of the ROI over the course of treatment. Surgical pathology was correlated with ADC data. RESULTS: Consecutive patients treated on a 0.35-T MRI radiotherapy system were evaluated. Patient A had the worst pathological response to NAC with a tumour regression score of 1 and was the only patient with a negative slope in the change of ADC values over the entire course of NAC, and during both the first and second half of NAC. The fDM from the first half of NAC for Patient A showed discrete dark areas in the tumour ROI, reflecting subregions with decreasing ADC values during NAC. Patient C had the most favourable pathological response to NAC with a Grade 3 response and was the only patient who had an increase in the slope in the change of ADC values from the first to the second half of NAC. CONCLUSION: DWI using a low-field MRI radiotherapy system for evaluating the responses to NAC is feasible. Advances in knowledge: ADC values obtained using a 0.35-T MRI radiotherapy system over the course of NAC for rectal cancer correlate with pathological responses.